Retinoid and tumor promoting agents are known to alter cell surface macro-molecules. These groups of agents exerted opposing actions on the availability of epidermal growth factor receptors and on the biosynthesis and secretion of procollagen in JB-6 cells, a cell line derived from mouse epidermis, and in 3T12 cells, a cell line of spontaneously-transformed mouse fibroblasts. Generally, the cells responded to retinoid treatment by an increase in adhesion, in epidermal growth factor receptor number and in the biosynthesis of procollagen, whereas the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate caused the opposite effects. Moreover, retinoids usually had a growth inhibitory effect, whereas the tumor promotor stimulated colony formation in soft agar in JB-6 cells. Inasmuch as retinyl phosphate has been shown to act as an intermidiate in glycosyl transfer reactions, changes in carbohydrate composition at the level of the cell surface were expected to occur as a result of retinoid treatment. Retinoid treated, more adhesive, fibroblasts were shown to contain relatively more of the complex type polysaccharide chains in glycoproteins at their cell surface, compared to control cells. A study of the cell surface glycoprotein fibronectin, released into the culture medium by chicken sternal chondrocytes after retinoic acid treatment, showed an increase in molecular weight compared to control. Analysis of the collagen binding domain of fibronectin from retinoid treated cultures showed a considerable increase in its molecular weight over control. The difference in molecular weight was abolished by tunicamycin, a known inhibitor of glycosylation. Moreover, Beta-endo-N-acetyl glycosaminidase H digestion of the 2-3H-mannose-labeled collagen binding domain of fibronectin showed that retinoic acid caused a relative increase in complex oligosaccharide chains of this glycoprotein, in agreement with the findings on fibroblast cell surface. Thus, retinoids may control cell surface properties by modulating the glycosylation of crucial molecules such as fibronectin, thus possibly affecting their retention on the cell and/or biological activity.